Description

Various genetically modified microorganisms that
over-express dioxygenase-type enzymes can be used for the large
scale production of compounds such as A (and known as
cis-1,2-dihydrocatechols) from the corresponding aromatic
precursor. These metabolites, which are almost invariably
obtained in near enantiomerically pure form, have served, over
many decades, as valuable starting materials in chemical
synthesis. The papers presented in this thesis by...[Show more] publication
reinforce this proposition.In order to appropriately
contextualize the work undertaken by the author, an extended
survey of the use of compounds such as A in total syntheses
undertaken by the Banwell Group (and within which the author
worked) is provided. Copies of the author’s four publications
(and, where relevant, the associated Supporting Information
documents) are then presented. The first publication (Publication
1) associated with this body of work represents an invited review
article and also serves to contextualise, albeit from a somewhat
broader perspective than given in the above-mentioned survey,
the work reported in the next parts of the thesis by describing
various of the contemporary ways in which homochiral and
microbially-derived cis-1,2-dihydrocatechols such as A have been
exploited as starting materials in the
stereochemically-controlled synthesis of a range of natural
products and their analogues.Publication 2 details syntheses of a
series of twenty-eight analogues of the phytotoxic
geranylcyclohexentriol (–)-phomentrioloxin A (B). These have
been prepared through cross-couplings of various enantiomerically
pure iodoconduritols or certain deoxygenated derivatives with
either terminal alkynes or borylated alkenes. Some of these
analogues display modest herbicidal activities and physiological
profiling studies suggest that one, C, inhibits photosystem II in
isolated thylakoids. Publication 3 is concerned with the
development of so-called chemoenzymatic total syntheses of the
natural product (+)-asperpentyn and the enantiomer of the
structure assigned to aspergillusol A. These syntheses start from
the enantiomerically pure cis-dihydrocatechol D, itself obtained
through the whole-cell biotransformation of
iodobenzene.Specifically, then, Publication 3 details the
establishment of a concise (five step) synthesis of
(+)-asperpentyn (E) and an eight-step reaction sequence leading
to compound F, the enantiomer of the structure, G, assigned to
the natural product aspergillusol A. Both routes employ the
enantiomerically pure cis-1,2-dihdrocatechol D as starting
material and use Sonogashira cross-coupling chemistry to install
the required enyne side-chain.On the other hand, Publication 4
describes syntheses of certain di- and mono-oxygenated
derivatives (e.g. H and I, respectively) as well as analogues
such as K-M of both the (–)- and (+)-enantiomeric forms of the
alkaloid galanthamine (J). All have been assessed for their
capacities to inhibit acetylcholinesterase but, in contrast to
the predictions from docking studies, none binds strongly to this
enzyme.